C-CAR066，一种新型全人源抗 CD20 CAR-T 疗法用于抗 CD19 CAR-T 疗法失败后的复发/难治性大 B 细胞淋巴瘤：一项 I 期临床研究

Managing large B-cell lymphoma (LBCL) that is refractory to or relapsed after chimeric antigen receptor (CAR)-T therapy remains a significant challenge.

Here we aimed to investigate the safety and efficacy of C-CAR066, an autologous fully human anti-CD20 specific CAR-T, for relapsed/refractory LBCL after failure of anti-CD19 CAR-T therapy. This first-in-human, single-arm, phase 1 study was conducted at two sites in China. Eligible patients had to be histologically confirmed with CD20-positive LBCL and must have received prior anti-CD19 CAR-T therapy. Patients received a single intravenous infusion of C-CAR066 at a target dose of 2. 0 10 6 or 3. 0 10 6 CAR-T cells/kg. The primary endpoint was the incidence of adverse events (AEs). As of October 10, 2023, 14 patients had received C-CAR066. The most common AEs of Grade 3 or higher were hematological toxicities.

Cytokine release syndrome occurred in 12 (85. 7%) patients, with only one was Grade 4 event. No patient experienced immune effector cell-associated neurotoxicity syndrome events. The overall response rate was 92. 9% with a complete response rate of 57. 1%. With a median follow-up of 27. 7 months (range, 3. 3-40. 9), the median progression-free survival and overall survival were 9.

4 months (95% CI, 2. 0 to NA) and 34. 8 months (95% CI, 7. 5 to NA), respectively. C-CAR066 demonstrated a manageable safety profile and promising efficacy in patients in whom prior anti-CD19 CAR-T therapies had failed, providing a promising treatment option for those patients. This trial was registered with ClinicalTrials. gov, NCT04316624 and NCT04036019.